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Trial registered on ANZCTR


Registration number
ACTRN12622000302752
Ethics application status
Approved
Date submitted
13/12/2021
Date registered
17/02/2022
Date last updated
17/02/2022
Date data sharing statement initially provided
17/02/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Impact of intra-tumour injection of OncoSil (32P) on vascularity, stromal integrity and response to chemotherapy in locally advanced pancreatic carcinoma
Scientific title
Impact of intra-tumour injection of OncoSil (32P) on vascularity, stromal integrity and response to chemotherapy in locally advanced pancreatic carcinoma
Secondary ID [1] 306031 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Unresectable Locally Advanced Pancreatic Carcinoma 324664 0
Condition category
Condition code
Cancer 322115 322115 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - OncoSil™
OncoSil™ is a brachytherapy medical device comprised of OncoSil™ Phosphorus-32 Microparticles and OncoSil™ Diluent. OncoSil is an active implantable (radiological) medical device intended for use in brachytherapy, where cancer is treated by the insertion of radioactive implants directly into the cancerous tissue. OncoSil™ has been designed to be injected directly into, and to deliver an average absorbed dose of 100 Gy to the target treatment tumour. In therapeutic use 98% of the radiation is delivered within 81 days. OncoSil is supplied sterile and is intended for single patient single-use.
When the baseline tumour volume is available to the Investigator and the study participant is deemed eligible, the investigator will prescribe the radioactivity dose to be implanted (mL). The purpose of OncoSil is to deliver radiation from Phosphorous-32 (32P) directly into the tumour to destroy cancer cells. The radiation particles will only travel a short distance (i.e. approximately 2.76 mm) inside the tumour and therefore very little radiation will leave the body.
Once consented participants are to receive either: (i) OncoSil plus concurrent Standard of Care (SOC) Chemotherapy - either FOLFIRINOX or gemcitabine + Abraxane; or (ii) SOC Chemotherapy alone – either FOLFIRINOX or gemcitabine + Abraxane.

Participants will be allocated to treatment arm that are correctly considered most appropriate given their individual circumstances. This will be at the discretion of their treating physician, oncologist, and investigator.

Implantation of OncoSil is performed using a disposable Endoscopic Ultrasound Fine Needle Aspiration (EUS-FNA) needle, loaded through the biopsy channel of the echoendoscope and slowly advanced through the gastric wall or duodenal wall into the target pancreatic tumour (avoiding vessels and avoiding damage to surrounding organs) using endoscopic ultrasound guidance.
The position of the needle tip within a tumour will be identified by endoscopic ultrasound localisation prior to injection. The Endoscopist, who will perform the procedure, will determine the needle placement intratumourally. The required amount of OncoSil is then implanted within the tumour by an Authorised User.
The anticipated duration of the procedure is 30-60 minutes. Participants in the OncoSil allocation group will only receive the procedure once as the product is single-use. The procedure visit is expected to occur approximately 4 weeks after commencement of chemotherapy.
Following implantation, participants will be observed for a minimum of four hours and, if stable and pain-free, will be discharged the same day. An overnight stay is optional and is at the discretion of the study doctor.
Once discharged from the endoscopy suite, the study doctor or a member of the research staff will direct participants to the Nuclear Medicine department to have a Bremsstrahlung Scan. This scan is performed to confirm radioactivity and positioning of the implant. The scan is expected to go for 40 minutes, and when this is complete the participant is free to leave the hospital.
Intervention code [1] 322430 0
Treatment: Devices
Comparator / control treatment
'Standard-of-care chemotherapy ONLY" group is the comparator.

The drug to be administered will be either FOLFIRINOX (FOL – calcium folinate, F – fluorouracil (5FU), IRIN – irinotecan, OX – oxaliplatin), or Gemcitabine + Abraxane (Gem-Nab).

Typically, the recommended dose for FOLFIRINOX regime is intravenous infusion of FOL 400 mg/m2, F 400 mg/m2, IRIN 180 mg/m2, and OX 85 mg/m2, administered on Day 1 and for about 2-4 hours, followed by continuous infusion of additional 2,400 mg/m2 of F over 46 hours, of each 14-day cycle.

Typically, the recommended dose for Gem-Nab regime intravenous infusion of 125 mg/m2 Abraxane and 1000 mg/m2 Gemcitabine, administered on Days 1, 8, and 15 of each 28-day cycle, and will be 30-60 minutes.

Cycle schedules are continuous until disease progression or unacceptable toxicity. The amount, duration, and frequency administered will vary and will be the discretion of your Oncologist; this will be the same whether you are participating in the study or not.
Control group
Active

Outcomes
Primary outcome [1] 329879 0
Safety / Tolerability of Device according to CTCAE V4.0 - as determined by the number of treatment emergent adverse events evaluated.
Timepoint [1] 329879 0
Collected from the time of signed informed consent until patient death or 104 weeks post last patient enrolment date, whichever is sooner.
Primary outcome [2] 329880 0
Identifying changes in tumour down-staging before and after OncoSil injection. Assessed with initial and interval CT and 18FDG PET-CT imaging. Successful tumour down-staging is defined as a reduction in tumour size (volume) that results in less or no vascular involvement and allows the tumour to be resected, as judged by the pancreatico-biliary surgeon. Tumour size determined from CT scans by a centralized radiological centre using standardized program.
Timepoint [2] 329880 0
Initial CT and PET-CT assessed at baseline screening, and follow up CT and PET-CT assessed at 12 weeks post-OncoSil implantation (approximately 16 weeks from baseline screening), to assess tumour size and disease activity changes. 8 Weekly Medical record review will also be assessed, up to 104 weeks post enrolment date.
Primary outcome [3] 329881 0
To identify changes in tumour vascularity before and after OncoSil injection. This is done by observing the tumour enhancement, produced by generating Time Intensity Curves via Endoscopic Ultrasound evaluation with 0.5ml of Contrast medium. The following parameters of Time Intensity Curves are assessed:
- Baseline intensity (dB), echo intensity before injection of contrast agent;
- Peak intensity (dB), echo intensity at the peak;
- Time to peak (s), time from injection of contrast medium to peak intensity;
- Intensity gain, echo intensity gain from baseline to peak intensity;
- I60, echo intensity 60s after injection of contrast medium;
- Reduction rate (%), the rate of reduction intensity from the peak to 60s.
Timepoint [3] 329881 0
Data for this assessment will be collected on the day of the procedure from EUS evaluation with contrast (before OncoSil implantation), and again approximately at 4 weeks post procedure with a repeat EUS evaluation with contrast.
Secondary outcome [1] 404147 0
Overall survival - Time to participant death from enrolment.. Data is collected via patient medical records and electronic medical records.
Timepoint [1] 404147 0
104 weeks post last patient first study visit.
Secondary outcome [2] 404148 0
Pain Scores - As measured at each study visit using the Numerical Rating scale (NRS)
Timepoint [2] 404148 0
Measured at each study visit for the duration of the study, These are to be collected at Screening, Procedure day (before injection of contrast agent and EUS procedure), and follow up visits post-procedure at week 4 and 12.
Secondary outcome [3] 404149 0
Technical success, defined as the ability to inject the target dose of OncoSil into the cancer mass without any spillage to the surrounding organ as assessed by the immediate Bremsstrahlung scans.
Timepoint [3] 404149 0
Bremsstrahlung scans are performed and assessed approximately 4 hours after implant.
Secondary outcome [4] 404697 0
Changes in tumour histopathology will be assessed by histology obtained from Endoscopic Ultrasound (EUS)-guided core biopsy specimens. [Note: This will be assessed as a Primary Outcome]
Timepoint [4] 404697 0
Data for this assessment will be collected on the day of the procedure (before implantation of OncoSil) and evaluated approximately 72 hours post-procedure. Second biopsy collection will be approximately at 4 weeks post procedure at follow-up EUS procedure and evaluated approximately 72 hours post-procedure. 8 Weekly Medical record review will also be assessed, up to 104 weeks post enrolment date.
Secondary outcome [5] 405812 0
Changes in tumour resectability will be assessed by histology obtained from Endoscopic Ultrasound (EUS)-guided core biopsy specimens. [Note: This will be assessed as a Primary Outcome]
Timepoint [5] 405812 0
Data for this assessment will be collected on the day of the procedure (before implantation of OncoSil) and evaluated approximately 72 hours post-procedure. Second biopsy collection will be approximately at 4 weeks post procedure at follow-up EUS procedure and evaluated approximately 72 hours post-procedure. 8 Weekly Medical record review will also be assessed, up to 104 weeks post enrolment date.

Eligibility
Key inclusion criteria
1. Study participants are greater than/equal to 18 years of age at screening.
2. Histologically or cytologically proven adenocarcinoma of the pancreas.
3. Unresectable locally advanced pancreatic carcinoma. Patients with technically resectable tumours (T1-T3) will also be eligible, if they are deemed unresectable due to medical comorbidities or refusal of surgery.
4. Pancreatic target tumour diameter of less than/equal to 6.0 cm (longest axis)
5. An ECOG Performance Status of 0 to 1 and Karnofsky Performance Status of 80 – 100.
6. Standard first line chemotherapy with FOLFIRINOX will be commenced within 14 days post enrolment, with OncoSil implantation to occur during the 4th week from commencement of chemotherapy.
7. Willing and able to complete study procedures within the study timelines.
8. Adequate renal function: serum creatinine less than 1.5 x upper limit of normal (ULN).
9. Adequate liver function: Serum SGOT/AST and serum SGPT/SLT less than 3 times ULN and serum bilirubin less than 1.5 times the ULN unless the patient is known to have prior Gilbert’s Syndrome.
10. Adequate bone marrow function: white blood cells (WBCs) greater than/equal to 3,000/mm3, absolute neutrophil count (ANC) greater than/equal to 1,500/mm3, haemoglobin greater than/equal to 9 g/dL, and platelets greater than/equal to 100,000/mm3.
11. Life expectancy of at least 3 months at the time of screening as judged by the investigator.
12. Not pregnant, and if of childbearing potential, agrees to use adequate birth control (hormonal or barrier method of birth control or abstinence) prior to study entry and during the study and agrees not to donate sperm or ova, for the duration of the study and 12 months post implantation of the investigational device.
13. Provide signed Informed Consent.
14. Technically feasible – tumour must be within reach of the EUS probe for fine needle injection
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Evidence of distant metastases
2. More than one primary lesion.
3. Any prior radiotherapy or chemotherapy for pancreatic cancer.
4. Use of other investigational agent at the time of screening, or within 30 days or five half-lives of Screening Visit 1, whichever is longer.
5. Pregnant or lactating.
6. History of malignancy, treated or untreated, within the past five years whether or not there is evidence of local recurrence or metastases, with the exception of basal cell carcinoma of the skin and cervical carcinoma in situ.
7. Evidence of tumour invasion into stomach, duodenum or peritoneum
8. In the opinion of the investigator, EUS directed implantation posing undue study participant risk. This includes:
(a) Where previous EUS-FNA was considered technically too difficult to perform;
(b) Imaging demonstrates multiple collateral vessels surrounding or adjacent to the target tumour within the pancreas;
(c)Presence (or significant risk) of varices near to the target tumour.
9. A known allergy or history of hypersensitivity to silicon, Phosphorus or any of the OncoSil™ components.
10. Patients who do not consent to chemotherapy
11. Actively on medication that increase bleeding risk (i.e. aspirin, clopidogrel, warfarin, NOAC)
12. Any other health condition that would preclude participation in the study in the judgment of the investigator.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/03/2022
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 21317 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 36202 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 310370 0
Hospital
Name [1] 310370 0
Royal Adelaide Hospital
Country [1] 310370 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
Port Road, Adelaide, SA 5000
Country
Australia
Secondary sponsor category [1] 311506 0
None
Name [1] 311506 0
Address [1] 311506 0
Country [1] 311506 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310023 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 310023 0
CALHN Research Office
RAH Clinical Trial Centre
Level 3, Royal Adelaide Hospital
Port Road
ADELAIDE SA 5000
Ethics committee country [1] 310023 0
Australia
Date submitted for ethics approval [1] 310023 0
Approval date [1] 310023 0
30/06/2020
Ethics approval number [1] 310023 0
HREC/19/CALHN/484

Summary
Brief summary
Who is it for?
You may be eligible for this study if you are 18 years or older, and have been diagnosed with locally advanced pancreatic cancer (LAPC),

Purpose of the study
To investigate the safety of an active implantable (radiological) medical device called OncoSil, when implanted into patients with pancreatic cancer who are receiving standard chemotherapy, and to evaluate the response on the tumour after implantation. This will be compared to those who receive standard chemotherapy alone.
Allocation to receive OncoSil treatment will be at the discretion of the investigator of the study, and your treating physician and oncologist.

Study Details
Participants that will receive the OncoSil treatment will undergo an Endoscopic Ultrasound, to accurately visualise the pancreas and assess tumour size. This will be performed under sedation and you are not likely to feel any pain during the process. The doctor guides the endoscope down the oesophagus, through the stomach and into the first part of the small intestine. The ultrasound is used to image the tumour in the pancreas. A fine needle is extended from the end of the endoscope into the pancreas and into the middle of the tumour. Once this needle is in an appropriate position within the tumour, a doctor will attach a syringe filled with OncoSil to the other end of the needle.

The doctor will slowly depress the plunger of the syringe so that the contents of the syringe are implanted into the tumour, the OncoSil syringe is removed. Another syringe containing a small amount of saline (salt water solution) is attached to the needle. This will flush any remaining OncoSil from the needle into the tumour. The saline syringe is removed. The endoscope is removed by carefully pulling it back up the oesophagus and out of your mouth. Following implantation, you will be observed for a minimum of four hours and, if stable and pain-free, you may be discharged the same day. You will be required to attend two follow up visits with you study doctor, which will occur 4 weeks and 12 weeks after the OncoSil procedure.

We hope this research will help provide further information on the safety and usefulness of this form of treatment for LAPC, and the results support further evaluation with larger trials.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 116218 0
Prof Nam Nguyen
Address 116218 0
Department of Gastroenterology and Hepatology,
Royal Adelaide Hospital,
Port Road,
Adelaide,
South Australia, 5000
Country 116218 0
Australia
Phone 116218 0
+61 8 7074 2124
Fax 116218 0
+61 8 7074 6192
Email 116218 0
quocnam.nguyen@sa.gov.au
Contact person for public queries
Name 116219 0
Mrs Romina Safaeian
Address 116219 0
Department of Gastroenterology and Hepatology,
Royal Adelaide Hospital,
Port Road,
Adelaide,
South Australia, 5000
Country 116219 0
Australia
Phone 116219 0
+61 8 7074 2189
Fax 116219 0
+61 8 7074 6192
Email 116219 0
romina.safaeian@sa.gov.au
Contact person for scientific queries
Name 116220 0
Mrs Romina Safaeian
Address 116220 0
Department of Gastroenterology and Hepatology,
Royal Adelaide Hospital,
Port Road,
Adelaide,
South Australia, 5000
Country 116220 0
Australia
Phone 116220 0
+61 8 7074 2189
Fax 116220 0
+61 8 7074 6192
Email 116220 0
romina.safaeian@sa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Ethics approval was not obtained to make IPD available. Individual information will be de-identified and will not be disclosed to the public.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.